How does CB1 receptor activity affect clinical seizures? 2 The agonistic activity of CB1 decreases cAMP by inhibition of adenyl cylase, induces potassium efflux by stimulating A type and G-protein coupled inward rectifying potassium channels; also, it decreases calcium influx by inhibiting voltage-dependent N and P/Q-type calcium channels. This diminishes neuronal hyperexcitability and may attenuate seizure frequency. It also ameliorates the spasticity and tremors of multiple sclerosis and Huntington’s disease in animal models. 7
There are two cannabinoid receptors: CB1 and CB2. The CB1 receptors are expressed predominantly at presynaptic sites in GABAergic neurons. 4 , 5 These receptors are present in high densities at neuronal terminals of the basal ganglia, cerebellum, hippocampus, neocortex, hypothalamus, and limbic cortex. 6 To a lesser extent, the CB1 receptors are located in periaqueductal gray, dorsal horns, and immune cells. The CB2 receptor is primarily focused towards the human immune system; when activated, they can affect inflammation and immunosuppression. CB2 presence is also documented in animal brain physiology.
ENDOCANNABINOID SYSTEM/MECHANISM OF ACTION
For those whose seizures remain uncontrolled without alternative conventional interventions available, medical marijuana has received anecdotal support, but only on an empirical basis. Any clinical trial is appropriate only in selected refractory cases and only when strictly monitored by a physician. Being illegal in many jurisdictions remains a concern.
Seizures affect the endocannabinoid system and the expression of CB1 protein in the animal hippocampus. 8 This increases the expression of CB1 receptors in the CA1 through CA3 regions of the hippocampus and is postulated to be the mechanism of action for epilepsy control.
“Everyone associates cannabis with getting stoned,” she says. “But that’s not what it is. It’s medicine.”
“No anxiety. No insomnia. No irritability. No heart palpitations. And most importantly, no seizures. I’ve never felt so good.”
That night, however, Leyland’s internal medicine alarm was never triggered and she stayed up with friends until 6 a.m. “I’ve never been able to stay up all night,” Leyland reveals. “That was something as a teenager I always used to struggle with—I was so jealous of friends who would watch the sunrise.” Lack of sleep automatically puts Leyland in what she calls a “danger zone” in terms of feeling like she’s going to have a seizure. “Considering I was so sleep deprived, it was very out of character for me to be able to feel well for that long on my feet. My brain felt normal, or what I would imagine someone without epilepsy would feel.”